ABSTRACT
Using a one-trial procedure, preweanling rats exhibit robust sensitization regardless of whether drug pretreatment and testing occur in the same or different environments. The purpose of the present study was to determine whether one-trial context-specific and context-independent sensitization of preweanling rats could be dissociated by varying the pretreatment dose of cocaine, by varying the pretreatment drug, or by minimizing interoceptive cues. In Experiments 1a and 1b, rats were pretreated with a broad dose range of cocaine (0-40 mg/kg) before placement in a novel activity chamber or the home cage. In Experiment 2, rats were pretreated with a locomotor-enhancing drug (e.g., methylphenidate, U50,488, or MK-801) before placement in a novel activity or anesthesia chamber. In Experiment 3, rats were anesthetized with isoflurane before cocaine administration to minimize the effects of interoceptive and injection cues. In all experiments, rats were challenged with cocaine on the test day (24 hr later), with locomotion being measured in activity chambers. Results showed that (a) the pretreatment dose of cocaine (10-40 mg/kg) did not differentially affect context-specific and context-independent sensitization; (b) cross-sensitization between methylphenidate and cocaine was observed in the context-specific condition, but not when using a context-independent procedure; and (c) sensitization was evident if injection and interoceptive cues were minimized. One possibility is that associative processes do not modulate the one-trial sensitization of preweanling rats. Alternatively, "unitization" may cause preweanling rats to treat the different environments as equivalent, thus permitting robust sensitization even when drug pretreatment and testing occur in different environments.
Subject(s)
Anesthetics, Local/pharmacology , Behavior, Animal/drug effects , Cocaine/pharmacology , Conditioning, Operant/drug effects , 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology , Analgesics, Non-Narcotic/pharmacology , Analysis of Variance , Animals , Animals, Newborn , Central Nervous System Stimulants/pharmacology , Dizocilpine Maleate/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Female , Locomotion/drug effects , Male , Methylphenidate/pharmacology , Motor Activity/drug effects , Neuroprotective Agents/pharmacology , Physical Stimulation/methods , Rats , Rats, Sprague-DawleyABSTRACT
RATIONALE: Preweanling rats, unlike adults, exhibit context-independent behavioral sensitization after a single pretreatment injection of cocaine. OBJECTIVE: The purpose of this study was to examine environmental factors modulating one- and three-trial sensitization in preweanling rats. METHODS: For preweanling rats, drug pretreatments occurred on postnatal day (PD) 17-PD 19 (experiment 1) or PD 19 (experiment 2). One set of rats was injected with cocaine (30 mg/kg) and placed in anesthesia ("small"), operant conditioning ("large"), or activity chambers for 30 min. Rats were returned to the home cage and injected with saline. Additional groups of rats were injected with saline and placed in small, large, or activity chambers for 30 min and then injected with cocaine after being returned to the home cage. Control groups were injected with saline at both time points. In separate experiments, rats were pretreated with cocaine or saline and restricted to the home cage. On PD 20, all rats were injected with cocaine (20 mg/kg) and placed in activity chambers where locomotor activity was assessed for 60 min. For comparison purposes, sensitization was also assessed in adult rats. RESULTS: Adult male and female rats exhibited only context-dependent sensitization, whereas preweanling rats showed context-independent sensitization in a variety of conditions (e.g., when pretreated with cocaine in various novel chambers or the home cage). CONCLUSIONS: These results suggest that nonassociative mechanisms underlying behavioral sensitization are functionally mature in preweanling rats, but associative processes modulating the strength of the sensitized response do not function in an adult-like manner during the preweanling period.
